EXCLUSION OF DEFECTS IN THE SKELETAL-MUSCLE SPECIFIC REGIONS OF THE DHPR ALPHA(1) SUBUNIT AS FREQUENT CAUSES OF MALIGNANT HYPERTHERMIA

The molecular defect predisposing to the majority of malignant hyperth ermia (MH) cases is unknown, although various point mutations in the r yanodine receptor gene (RYR1) have been associated with susceptibility in a small proportion of cases. We report here that one of these, the Arg163Cys substitution, does not cosegregate with MH susceptibility. Comparison of cDNA sequences encoding the skeletal muscle specific com ponents of the dihydropyridine receptor a, subunit between MH suscepti ble (MHS) and MH non-susceptible (MHN) patients was made in subjects w ithout the reported MH Linked RYR1 mutations. There were no difference s within the sequence encoding the II-III loop or the IS3/IS3-IS4 segm ent, excluding defects in these functional segments of the alpha(1) su bunit as frequent causes of MH.